Cimifugin suppresses allergic inflammation by reducing epithelial derived initiative key factors via regulating tight junctions.

Abstract

Cimifugin is a bioactive component of Saposhnikovia divaricata, a Chinese herb for treating allergy. Our previous studies demonstrated that cimifugin inhibited allergic inflammation efficiently. This study aims to determine the mechanism of cimifugin on epithelial cells in allergic inflammation. Mice were sensitized and challenged with FITC to establish type 2 atopic dermatitis (AD) model. The initial stage of AD model, in which mice were just sensitized with FITC, was established in vivo and immortalized human epidermal (HaCaT) cells were utilized in vitro. Initiative key cytokines, TSLP and IL-33, were measured by ELISA, the junctions in ECs were observed by electron microscopy and TJs (CLDN-1, occludin and CLDND1) were assessed by Western blot, immunohistochemistry and immunofluorescence. The results showed that TSLP and IL-33 were inhibited significantly by cimifugin in the initial stage of AD model. Simultaneously, cimifugin reduced the separated gap among the epithelial cells and increased the expression of TJs. Similar effects on TSLP/IL-33 and TJs were obtained in vitro. The effect of cimifugin on TSLP decreased significantly when expression of CLDN1 was interfered with siRNA and this implied cimifugin inhibits initiative cytokines through restoring TJs. Furthermore, cimifugin administered only in the initial stage obviously attenuated the ultimate allergic inflammation, which indicate that impacts of cimifugin in the initial stage on TSLP/IL-33 and TJs are sufficient for suppressing allergic inflammation. This study not only revealed the mechanisms of cimifugin, but also indicated the possibility of initiative key cytokines and TJs as therapeutic targets.

• Authors: Xiaoyu Wang, Xiaoyan Jiang, Xi Yu, Hailiang Liu, Yu Tao, Guorong Jiang, Min Hong
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 21 Issue 11 Pg. 2926-2936 (Nov 2017) ISSN: 1582-4934 [Electronic] England
• PMID: 28597545 (Publication Type: Journal Article)
• Copyright: © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Chemical References

• Anti-Allergic Agents
• Chromones
• Claudin-1
• Claudins
• Cldn1 protein, mouse
• IL33 protein, human
• Immunoglobulins
• Interleukin-33
• Occludin
• Ocln protein, mouse
• Receptors, Cytokine
• Tslpr protein, mouse
• cimifugin
• Fluorescein-5-isothiocyanate

Topics

• Animals
• Anti-Allergic Agents (isolation & purification, pharmacology)
• Apiaceae (chemistry)
• Cell Line, Transformed
• Chromones (isolation & purification, pharmacology)
• Claudin-1 (genetics, metabolism)
• Claudins (genetics, metabolism)
• Dermatitis, Atopic (chemically induced, drug therapy, genetics, pathology)
• Disease Models, Animal
• Fluorescein-5-isothiocyanate (administration & dosage)
• Gene Expression Regulation
• Humans
• Immunoglobulins (genetics, metabolism)
• Inflammation
• Interleukin-33 (genetics, metabolism)
• Keratinocytes (drug effects, metabolism, pathology)
• Mice
• Mice, Inbred BALB C
• Occludin (genetics, metabolism)
• Receptors, Cytokine (genetics, metabolism)
• Signal Transduction
• Tight Junctions (drug effects, genetics, pathology)